Gemcitabine Active in Patients With Metastatic Breast Cancer

July 1, 2001

In two phase II clinical trials presented at the annual meeting of the American Society of Clinical Oncology, researchers found that gemcitabine (Gemzar) alone and in combination with docetaxel

In two phase II clinical trials presented at the annualmeeting of the American Society of Clinical Oncology, researchers found that gemcitabine (Gemzar) alone and in combinationwith docetaxel (Taxotere) was associated with a high level of activity and anacceptable toxicity profile in women with previously treated refractorymetastatic breast cancer.

Standard treatment in the United States for patients withanthracycline-refractory metastatic breast cancer has been sequentialsingle-agent therapy, often starting with taxanes—ie, docetaxel or paclitaxel(Taxol). Data from these trials suggest that gemcitabine alone or in combinationwith docetaxel should be investigated as an alternative for patients whopreviously received anthracycline-based and in some cases taxane-basedchemotherapy.

Gemzar in Taxane- or Anthracycline-Resistant Breast Cancer

In one of the trials, researchers evaluated the efficacy andtolerability of gemcitabine in 22 women with metastatic breast cancer resistantto taxane- or anthracycline-based therapy. The mean age of study participantswas 55 years. All had received two or fewer previous treatment regimens formetastatic disease and developed disease progression despite either taxane- oranthracycline-based therapy. All had measurable progressive lesions with noevidence of brain metastasis.

During each 28-day treatment cycle, patients were givengemcitabine intravenously (IV) at a dose of 1,000 mg/m2 on days 1, 8, and15. Patients with symptomatic bone lesions also received radiotherapy. At theend of every three cycles, patients were restaged and response was evaluatedusing World Health Organization (WHO) criteria.

The overall response rate was 23%, with one patientdemonstrating a complete response and four patients, a partial response. Stabledisease was achieved by 6 patients (27.2%), while 11 (50%) showed evidence ofdisease progression. Hematologic toxicity was manageable and did not require theuse of growth factors. The main side effect was an influenza-like syndrome withfever (45.4%) and fatigue (36.3%).

"While the majority of women with metastatic breast cancerare treated initially with taxanes, many fail to respond, eventually progress,or experience dose-limiting toxicity," said Andrew D. Seidman, MD,associate attending physician, Breast Cancer Medicine Service, MemorialSloan-Kettering Cancer Center in New York. "Developing effective drugs thathave acceptable toxicity is a high priority in treating breast cancer patients,many of whom are middle-aged and lead active lives while undergoingchemotherapy. Results from this study and previously published studies suggestthat gemcitabine deserves attention and further investigation in this patientpopulation."

Multicenter Trial of Combination Therapy

In a multicenter phase II trial, researchers evaluated theefficacy and safety of the gemcitabine/docetaxel combination as second-linechemotherapy in 30 women with metastatic breast cancer who failed to respond toanthracycline-based therapy. The median age of participants was 57 years. Allhad metastatic breast cancer, with 23 showing evidence of visceral disease. Allalso had anthracycline-resistant disease. Prior to the start of the trial, 13women had received one previous chemotherapy regimen, while 17 women hadreceived two or more previous regimens. Moreover, 26 patients had received prioranthracycline-based chemotherapy, while 4 had received taxane-based chemotherapy(5 as adjuvant).

As part of each treatment cycle, patients were given gemcitabine(1,000 mg/m2 IV over 30 minutes on days 1 and 8) and docetaxel (80mg/m2 IV over1 hour on day 8). The cycle was repeated every 3 weeks, and a total of 148cycles were administered.

The overall response rate was 60%, with two patientsdemonstrating a complete response and 18 patients, a partial response. Themedian time to disease progression was 6 months. The median overall survivalafter 6 months has not yet been determined. Treatment-related adverse eventswere mild to moderate in intensity. They included leukopenia (31%), neutropenia(33%), anemia (11%), hair loss (93%), and mucositis (7%).